We propose to develop a birth control vaccine for women which blocks fertilization and is effective, safe and widely acceptable. The vaccine uses the sperm surface protein PH-20, the only sperm protein shown to give 100% effective contraceptive in an animal model. Since we have cloned and expressed cDNA for human PH-20, we propose here efficacy and safety testing in primates to be followed by a Phase I clinical trail. Important individual aims include: 1. Test if 100% effective contraception is obtained in female macaque monkeys immunized with macaque PH-20. A. Compare contraceptive effectiveness with different adjuvants. B. Compare contraceptive effectiveness with recombinant macaque PH-20 made in different expression systems. 2. Determine if immunization with PH-20 can be used on multiple occasions in a female monkey to provide contraception. 3. Perform pre-clinical toxicological tests agreed upon with the FDA in order to obtain an investigational new drug application (IND). A. Confirm that PH-20 is a sperm-specific protein in macaques and humans. B. Test if anti-PH-20 antisera from infertile macaques show cross- reactivity with any female tissues. C. Study the offspring of PH-20 immunized macaques who have regained fertility to determine if they show any abnormalities. 4. Perform Phase I clinical trial immunizing sterile women with recombinant human PH-20 to assess safety.